PB2344: STR-LOCI ALLELE IMBALANCE AT 9P24.1 AND PD-L1 EXPRESSION IN PRIMARY MEDIASTINAL B-CELL LYMPHOMA.
Authors: Runiza Abdurashidova, Natalia Risinskaya, Yana Mangasarova, Elena Nikulina, Irina Shupletsova, Anna Yushkova, Alla Kovrigina, Vadim Surin, Hunan Julhakyan, Andrey Sudarikov
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Primary mediastinal B-cell lymphoma (PMBCL) is the only non-Hodgkin’s lymphoma variant responding to immune checkpoint (ICP) therapy approximately in half of the cases. However, no molecular markers predicting response to ICP have been described so far. In this study, we assessed the incidence of the loss of heterozygosity (LOH), elevated microsatellite alteration at selected tetranucleotides (EMAST) in tumor genomes and PD-L1 expression level in tumor cells of PMBCL patients. Primary mediastinal B-cell lymphoma (PMBCL) is the only non-Hodgkin’s lymphoma variant responding to immune checkpoint (ICP) therapy approximately in half of the cases. However, no molecular markers predicting response to ICP have been described so far. In this study, we assessed the incidence of the loss of heterozygosity (LOH), elevated microsatellite alteration at selected tetranucleotides (EMAST) in tumor genomes and PD-L1 expression level in tumor cells of PMBCL patients. Aims: To analyze possible association between STR-loci AI in 9p24.1 and PD-L1 expression level in tumor cells of PMBCL patients. Methods: DESIGN: Two STR-loci (gt)n and (ttat)m at 9p24.1 of the DNA of tumor cells were analyzed on a cohort of 67 PMBCL patients admitted to the National Medical Research Center for Hematology (Moscow, Russia) from 2013 to 2022. For thirty patients, STR data were compared with PD-L1 expression assessed by immunohistochemistry (antibodies Cell Marque, clone 28-8, ER2-pH 9 Leica, BOND-MAX) SETTING: DNA was isolated from tumor biopsy samples taken at diagnosis. Control DNA samples were taken from the blood of patients in complete remission or from the buccal epithelium. STR-analysis for AI was done by PCR with original primers. The fragment analysis was performed on ABI3130 Genetic Analyzer. PATIENTS: Inclusion criteria: de novo diagnosed PMBCL patients. Exclusion criteria: pretreatment. Results: Heterozygosity level for (gt)n locus was 40 out of 67 patients (59,7%), AI was found in 22 out of 40 (59.7%). Heterozygosity level for (ttat)m locus was 48 out of 67 patients (71,6%), AI was found in 27 out of 48 (56,2%). Five patients turned out to be homozygous for both loci. No patients were found with AI at one locus and a normal heterozygous variant at the second locus. PD-L1 expression in tumorс cells was evaluated for thirty patients. In seven patients with aberrant STR loci, PD-L1 expression was found in 75%-100% of tumor cells. Nine patients with AI in 9p24.1 did not have PD-L1 positive cells. Four patients with PD-L1 expression did not have AI at 9p24.1. Summary: The high incidence of AI in the 9p24.1 locus indicates its possible involvement in the pathogenesis of PMBCL. The association between AI and PD-L1 expression in tumor seem to be independent events, but a study on an extended cohort of patients is needed.Keywords: Immunohistochemistry, B cell lymphoma, Diffuse large B cell lymphoma